We propose to study the mechanism of neurodegeneration in mice caused by paralytogenic wild mouse type C virus. Our approach to this long-term goal includes: (1) determination of mode of replication of the neurotropic type C virus in mouse neurons, (2) determination of viral gene expression, both at the level of RNA and proteins in isolated neurons of paralyzed and nonparalyzed viremic mice, and (3) examination of the role of subvirion components in membrane damage or alteration, and degeneration of neurons. Major analytical techniques including DNA-DNA hybridization, radioimmunoassay, membrane receptor binding assay, immunofluorescent and immunoperoxidase staining, etc., will be used in the present investigation. It is expected that our study on virus replication and gene expression in neurons will provide basic information on the mechanism of injury to neurons of mice by paralytogenic ecotropic viruses.